scholarly journals Hypoxia-Inducible Factors as Essential Regulators of Inflammation

2010 ◽  
pp. 105-120 ◽  
Author(s):  
Hongxia Z. Imtiyaz ◽  
M. Celeste Simon
Keyword(s):  
Hypoxia Inducible Factors

Pan-Cancer Analysis of Expression, Mutation and Prognosis for Hypoxia-Inducible Factors (HIFs) and Their Regulators

2020 ◽  
Author(s):  
Jingwei Liu ◽  
Hao Li ◽  
Min Guo ◽  
Jun-ling Ren ◽  
Ling Ren ◽  
...  
Keyword(s):  
Hypoxia Inducible Factors ◽  
Pan Cancer

scholarly journals Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592098707
Author(s):  
Carolina Méndez-Blanco ◽  
Paula Fernández-Palanca ◽  
Flavia Fondevila ◽  
Javier González-Gallego ◽  
José L. Mauriz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Tumor Size ◽  
Vasculogenic Mimicry ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Hypoxia Inducible Factors ◽  
Free Survival ◽  
Node Metastasis ◽  
Clinicopathological Significance

Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.

SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

Nature ◽  
2012 ◽  
Vol 487 (7407) ◽  
pp. 380-384 ◽  
Author(s):  
Marco Montagner ◽  
Elena Enzo ◽  
Mattia Forcato ◽  
Francesca Zanconato ◽  
Anna Parenti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Hypoxia Inducible Factors

Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair

2021 ◽  
Vol 218 (9) ◽  
Author(s):  
Matthew DeBerge ◽  
Connor Lantz ◽  
Shirley Dehn ◽  
David P. Sullivan ◽  
Anja M. van der Laan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Tissue Repair ◽  
Myeloid Cell ◽  
Selective Inhibition ◽  
Mitochondrial Metabolism ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Ischemic Tissue ◽  
Anti Inflammatory ◽  
Parenchymal Cells

Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.

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